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Introduction:The prevalence of both aortic stenosis (AS) and dementia increases with age, but studies evaluating in-hospital outcomes and readmission risk after transcatheter aortic valve replacement (TAVR) in patients with dementia are scarce.Hypothesis:The presence of dementia is associated with higher rates of adverse in-hospital outcomes and readmissions following TAVR.Methods:Using the National Readmissions Database 2017-2018, we identified all admissions for TAVR in patients with AS and stratified them to those with and without dementia. We assessed delirium and falls in hospital using multivariable logistic regression, and 90-day readmissions using multivariable Cox proportional-hazard modeling, adjusted for demographics, comorbidities, hospital characteristics, primary payer, median income, and elective admission status.Results:Among 48,923 TAVR procedures, 2,192 (4.5%) were performed in patients with dementia. Patients with dementia experienced higher odds of delirium (adjusted odds ratio [aOR] 4.50, 95% confidence interval [CI] 3.35-6.05, p<0.01) and fall in hospital (aOR 2.34, 95% CI 1.39-3.95, p<0.01) during hospitalization for TAVR. Patients with dementia also experienced an increased hazard of 90-day readmission (adjusted hazard ratio 1.14, 95% CI 1.04-1.25, p<0.01) (Figure 1). Causes of 90-day readmission were mostly non-cardiovascular.Conclusions:Patients with dementia undergoing TAVR suffered from increased odds of delirium and falls, with a higher hazard of 90-day readmission after discharge. These findings should be integrated into shared decision-making before elective TAVR.

Introduction:Guideline-recommended medical therapy (GDMT) for cardiovascular risk reduction remains sub-optimally prescribed in patients with peripheral artery disease (PAD). To begin addressing this issue, it is key as a health system to be able to monitor electronic health record (EHR)-based real-world data to assess GDMT usage rates and its association with long-term mortality and amputation.Methods:We included all patients with PAD who underwent peripheral vascular interventions (PVI) across the Yale New Haven Health System in 2016-2022. GDMT at PVI discharge was defined as having all 3 of: angiotensin converting enzyme inhibitor/angiotensin receptor blocker (if hypertensive), antiplatelet, and statin. Propensity scores were calculated based on age, sex, race, ethnicity, and Elixhauser comorbidities. Inverse probability weighted Cox regression models with a random effect for site and provider were constructed to evaluate the relationship between GDMT and 2-year mortality and major amputation.Results:A total of 3,741 patients with PAD underwent PVI. The average age was 72.3 (± 12.9) years, and 39% were female. GDMT rates at PVI discharge ranged from 24% to 40% during the study period. Lack of GDMT at discharge had a statistically insignificant association 2-year mortality risk (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 0.98-1.50, p=0.07; figure top) and a significant positive association with 2-year major amputation risk (HR: 2.73, 95% CI:1.51-4.94, p<0.001; figure bottom).Conclusions:This study leveraged system-wide EHR data to study GDMT use and its association with mortality and major amputation, which may serve as a metric for quality of PAD care.

Introduction:Current guidelines for sodium reduction focus on total daily sodium consumption (<2300 mg/d) for an intake of 2100 kcal. However, calorie consumption varies substantially. Here, we quantify mean sodium intake, calorie intake, and sodium density across demographic groups in the US and over time.Hypothesis:We hypothesized that, compared to sodium density, total sodium may overestimate adherence to sodium recommendations, especially in older adults.Methods:In the National Health and Nutrition Examination Survey (NHANES), weighted mean sodium and energy intake was estimated in US adults as the average of two 24-hour dietary recalls. Sodium density was calculated as the mg of sodium per 1,000 kcal consumed. The prevalence of adherence to sodium intake (<2300 mg/d) and sodium density (<1.1 mg/kcal) limits was quantified by age group, self-reported sex, self-reported race/ethnicity, Calorie level (<2100 kcal, ≥2100 kcal), and self-reported high blood pressure. Adherence prevalence estimates were compared between 2005-2006 and 2015-2016 survey periods by logistic regression adjusted for age, sex, and race/ethnicity.Methods:In 2015-2016, 24.8% of the US population (mean age 38 yr, 51% female, 12% black) adhered to the recommended <2300 mg/d sodium intake, but only 5.6% achieved the recommended 1.1 mg/kcal sodium density (Table). In 2005-2006, these figures were 26.5% and 8.9%, respectively. While there was no change in adherence by total sodium consumption (P = 0.11), adherence by sodium density was significantly lower in 2015-2016 than 2005-2006 (P < 0.001). The difference in adherence between total sodium and sodium density goals was greater among older adults (≥70 years), women, Hispanic adults, and adults consuming <2100 kcal per day.Conclusions:In 2015-2016, <6% of US adults consumed sodium densities at recommended levels. The prevalence of those achieving these goals is lower compared to 10 years prior. Further efforts to regulate population sodium intake are urgently needed.

Introduction:Obesity is strongly associated with elevated serum uric acid (SUA), a hypothesized mediator of cardiovascular disease. In observational studies, weight loss is associated with lower SUA. However, trial evidence on weight loss and SUA is lacking.Hypothesis:We hypothesized that in a randomized, controlled setting, intentional weight loss would reduce SUA.Methods:The Survivorship Promotion In Reducing IGF-1 Trial (SPIRIT) was a three-arm, parallel trial of overweight or obese adult cancer survivors that compared the effects of a coach-directed weight loss intervention or metformin to self-directed weight loss (ref) on insulin growth factor-1 (IGF-1) over a 1-year period. Participants in the coach-directed arm underwent behavioral-based telephonic coaching with web-based support to promote healthy lifestyle and weight loss, targeting a 5% weight loss in the first 6 months. Participants assigned metformin received up to 2,000 mg daily. In our study, SUA was measured in specimens collected at baseline, 3-months, 6-months, and 12-months.Results:There were 121 participants, with a mean age of 60 years (standard deviation [SD]: 9), and a mean body mass index (BMI) of 35 kg/m2(SD: 5). Compared to the self-directed group, coach-directed weight loss reduced BMI by 0.6 kg/m2(95% CI: 0.1, 1.1) and metformin reduced BMI by 0.9 kg/m2(95% CI: 0.4, 1.5) over 12 months. However, compared to the self-directed group, coach-directed weight loss significantly increased SUA by 0.3 mg/dL (95% CI: 0.1, 0.6) over 12 months, while metformin did not significantly affect SUA (0.2 mg/dL; 95% CI: -0.04, 0.5). The increase observed with the coach-directed weight loss intervention occurred primarily within the first 3 months of the intervention (Figure).Conclusions:Contrary to our expectations, intentional weight loss increased SUA in the short-term. These results question weight loss as a strategy for SUA reduction. Studies testing the long-term effects of weight loss on SUA are needed.

Introduction:The Dietary Approaches to Stop Hypertension (DASH) diet, a carbohydrate rich diet, has low adherence nationally despite its cardiovascular risk benefits. We examined the effects of carbohydrate amount and glycemic index [GI] on qualitative aspects of diet acceptability and considered their impact on diet adherence.Hypothesis:Higher carbohydrate and GI diets would increase hunger, decrease diet satisfaction, and increase gastrointestinal symptoms.Methods:OmniCarb was a randomized, crossover trial of 4 diets in overweight/obese adults without diabetes or cardiovascular disease (n=163). Diets varied by carbohydrate amount (40% vs 58% kcal) and GI (?65 vs ?45). Participants consumed each diet over four 5-week periods, separated by 2-week washout periods. Participants rated hunger, diet satisfaction, and gastrointestinal symptoms (diarrhea, constipation, bloating, nausea, and heartburn) upon completing each diet period.Results:Participant mean age was 53 years; 52% were women, 50% were non-Hispanic black, and 56% were obese. Relative to baseline diets, intervention diets decreased heartburn, increased diarrhea, increased bloating, and did not affect constipation or nausea. Compared to a low carbohydrate diet, a high carbohydrate diet increased hunger (RR=1.16, 95% CI 1.04-1.30), increased diet satisfaction (RR=1.10, 95% CI 1.01-1.20), and increased heartburn (RR=1.49, 95% CI 1.09-2.04). Compared to a low GI diet, a high GI diet did not affect hunger (RR=0.92, 95% CI 0.83-1.02), decreased diet satisfaction (RR=0.83, 95% CI 0.75-0.92), and did not affect heartburn (RR=0.89, 95% CI 0.70-1.13). Between intervention diet differences for diarrhea/loose stools, constipation, bloating, and nausea symptoms were non-significant.Conclusions:In the context of DASH type diets, higher carbohydrate amount and lower GI may increase hunger, diet satisfaction, and heartburn. These findings may inform strategies to improve diet adherence.

Introduction:Plasma lactate is a marker of non-oxidative glucose metabolism that is associated with progression to diabetes. We determined the effect of carbohydrate amount (%kcal) and quality (i.e. glycemic index [GI]) on plasma lactate.Hypothesis:We hypothesized that low GI (<45 [g] vs high ?65 [G]), and low %kcal from carbohydrate (40% kcal [c] vs high 58% kcal [C]) would reduce lactate levels.Methods:We measured lactate in stored specimens of OmniCarb, a randomized, crossover trial of 4 different diets in overweight or obese adults without diabetes or cardiovascular disease (n=163). The four diets were high carbohydrate+high GI (CG, ref), high carbohydrate+low GI (Cg), low carbohydrate+high GI (cG), and low carbohydrate+low GI (cg). Participants (n=163) consumed each of the 4 diets over a 5-week period, separated by 2-week washout periods. Plasma lactate levels were measured at baseline and at the end of each 5-week period.Results:Mean age was 53 years, with 52% female and 40% African-American. In the setting of high carbohydrate amount, reducing GI lowered plasma lactate by 0.08 mmol/L (Cg vs CG; 95% confidence interval [CI] -0.16, 0.00; P= 0.06; Figure).In the setting of high GI, reducing carbohydrate amount lowered plasma lactate by 0.10 mmol/L (cG vs CG; CI -0.19, -0.02; P= 0.02). The combined effect of reducing GI and carbohydrate proportion in the diet (cg vs CG) was similar to reducing either (cg vs CG: -0.08; CI -0.16, 0.00; P= 0.04) . All four diets reduced plasma lactate compared to baseline. Compared to baseline, reducing both GI and carbohydrate amount lowered lactate level by -0.18 mmol/L (cg vs baseline; CI -0.26, -0.11; P< 0.01).Conclusions:Compared to a diet with high GI and high carbohydrate amount, diets with low GI and/or low carbohydrate amount reduced plasma lactate, a marker of non-oxidative glycolysis and diabetes risk. Whether this change in lactate reduces diabetes risk in the long term should be examined. ClinicalTrials.gov:NCT00608049

Introduction:Cardiovascular death is the leading cause of mortality in patients on hemodialysis. Traditional risk factors such as diabetes and hypertension do not fully account for this excess risk. Toxic metabolites that accumulate in renal failure may be responsible for accelerated cardiovascular disease, but these metabolites remain undefined.Hypothesis:The goal of this pilot study was to determine if an untargeted metabolomic approach could identify metabolites associated with cardiac death in dialysis patients.Methods:In this matched case-control study nested in the HEMO study, cases experienced cardiac death vs. were alive, respectively, at 12 months after enrollment. Cases and controls were matched on sex, race, diabetes, cardiac disease, age, and albumin. Cardiac death included death from ischemic heart disease, heart failure, and arrhythmias. Serum samples frozen at the 4 month visit were profiled by mass spectrometry. Conditional logistic regression assessed each metabolite’s association with cardiac death.Results:A total of 47 cases and 47 controls were studied. 777 metabolites available for analysis after data preprocessing. At the p<0.005 threshold, several metabolites were positively associated with cardiac death, and several metabolites were negatively associated with cardiac death. However, no metabolite had significant associations using false discovery rate thresholds.Conclusions:Our study is an example of the use of metabolomics as a strategy for identification of metabolites that may explain the high risk of cardiac death in patients undergoing hemodialysis.Figure 1: Odds ratio for 1-year risk of cardiac death per doubling of metabolite level for each metabolite in the HEMO Study